The aim of the tutorial is to run Brownian dynamics simulations
of protein-protein association and to visualize the trajectories
of the proteins during these simulations.
- Protein-protein association is the most ubiquitous event in protein
function. Its rate is relevant for the function of proteins.
- When proteins must find one another by diffusion in order to associate,
the speed of association is limited by the bimolecular diffusional
association rate.
- In Brownian dynamics simulations (3), the diffusional motion of
proteins is generally modelled by assuming them to be rigid bodies
and
their interaction with solvent molecules is modeled implicitly
by random forces experienced by proteins due to collisions with water
molecules.
- During BD simulations, proteins may interact with one another by
exclusion and electrostatic forces. Attractive electrostatic forces
may result in
fast association rates that are sensitive to mutation of the protein
or to
changes in ionic strength. Electrostatic forces are computed from a
Poisson-Boltzmann continuum model under the effective charge
approximation (6).
- Brownian dynamics simulations allow prediction of the association
rates (1,5).
Association rates are derived by monitoring during the diffusional
motion
how close the proteins approach the target position.
For these simulations, you will use the SDA (Simulation of Diffusional
Association)
Program (2) written at EMBL
(see: http://www-z.embl-heidelberg.de:8080/ExternalInfo/wade/pub/soft/SDA).
Protein electrostatic potentials will be computed with the UHBD (University
of
Houston Brownian Dynamics) program and used as input for the Brownian
dynamics simulations with SDA.
Literature:
-----------
1. Gabdoulline,R.R. and Wade,R.C.
Simulation of the Diffusional Association of Barnase
and Barstar
Biophys. J. (1997) 72, 1917-1929
2. R.R. Gabdoulline, R.C. Wade. (1998) Methods, 14, 329-341.
Brownian dynamics simulation of protein-protein
diffusional encounter.
3. J.D. Madura, J.M. Briggs, R.C. Wade, R. Gabdoulline. (1998)
in The Encyclopedia of Computational Chemistry,
Schleyer, P.v. R.;
Allinger, N. L.; Clark, T.; Gasteiger, J.; Kollman,
P. A.;
Schaefer III, H. F.; Schreiner, P. R., Eds.;
John Wiley Sons, Chichester, 1998 Brownian
dynamics.
4. http://www-z.embl-heidelberg.de:8080/ExternalInfo/wade/pub/soft/SDA
5. Gabdoulline,R.R. and Wade,R.C. (2001) J. Mol. Biol. 306, 1139-1155.
Protein-protein Association: Investigation of Factors
Influencing Association
Rates by Brownian Dynamics Simulations
6. Gabdoulline,R.R. and Wade,R.C. (1996) J. Phys. Chem. 100, 3868-3878.
Effective charges for Macromolecules in Solvent